The influence of optimization target selection on the structure of arterial tree models generated by constrained constructive optimization

The computational method of constrained constructive optimization was used to generate complex arterial model trees by optimization with respect to a target function. Changing the target function also changes the tree structure obtained. For a parameterized family of target functions a series of trees was created, showing visually striking differences in structure that can also be quantified by appropriately chosen numerical indexes. Blood transport path length, pressure profile, and an index for relative segment orientation show clear dependencies on the optimization target, and the nature of changes can be explained on theoretical grounds. The main goal was to display, quantify, and explain the structural changes induced by different optimization target functions.     

Diverse reactions catalyzed by naphthalene dioxygenase fromPseudomonas sp strain NCIB 9816

Naphthalene dioxygenase (NDO) fromPseudomonas sp strain NCIB 9816 is a multicomponent enzyme system which initiates naphthalene catabolism by catalyzing the addition of both atoms of molecular oxygen and two hydrogen atoms to the substrate to yield enantiomerically pure (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene. NDO has a relaxed substrate specificity and catalyzes the dioxygenation of many related 2- and 3-ring aromatic and hydroaromatic (benzocyclic) compounds to their respectivecis-diols. Biotransformations with a diol-accumulating mutant, recombinant strains and purified enzyme components have established that in addition tocis-dihydroxylation, NDO also catalyzes a variety of other oxidations which include monohydroxylation, desaturation (dehydrogenation),O-andN-dealkylation and sulfoxidation reactions. In several cases, the absolute stereochemistry of the oxidation products formed by NDO are opposite to those formed by toluene dioxygenase (TDO). The reactions catalyzed by NDO and other microbial dioxygenases can yield specific hydroxylated compounds which can serve as chiral synthons in the preparation of a variety of compounds of interest to pharmaceutical and specialty chemical industries. We present here recent work documenting the diverse array of oxidation reactions catalyzed by NDO. The trends observed in the oxidation of a series of benzocyclic aromatic compounds are compared to those observed with TDO and provide the basis for prediction of regio- and stereospecificity in the oxidation of related substrates. Based on the types of reactions catalyzed and the biochemical characteristics of NDO, a mechanism for oxygen activation by NDO is proposed.     

A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa

Background

Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC).

Methods

In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms.

Outcomes

The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed.

Results

Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention.

Conclusions

This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy.

Trial Registration

www.Controlled-Trials.com ISRCTN22851337     

Nuclear DNA changes within Helianthus annuus L.: origin and control mechanism

Summary Previous results suggested that the amount of nuclear DNA varies in one and the same progeny of Helianthus annuus, depending on the head portion in which seeds have developed. Accordingly, cytophotometric determinations were carried out in a selfed line, after Feulgen-staining, to obtain information on the developmental stages at which DNA changes are produced and on the mechanism controlling the variation. It was found that the Feulgen absorption values of mitotic prophases in immature anthers and pistils and of meiotic prophases I are the same in any flower of the head. In contrast, the Feulgen/DNA contents of early prophases in heart-shaped embryos differ significantly, increasing from those developing at the centre of the head to those developing at its periphery, and remaining unchanged in each embryo during further development and seed germination. Variations in the number of chromosomes do not account for the differences observed in nuclear DNA contents in which sequences comprised in heterochromatic nuclear regions are involved. The Feulgen absorption values of seedlings obtained from seeds developed in different portions of single heads increase or diminish starting from those found in the mother plant. This depends on whether these latter are relatively low or high and on the gradient of seed location in the head. The variation occurring within each single progeny covers the whole range existing within the line.     

Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme

We report the nucleotide sequence of a cloned cDNA, pMTS-3, that contains a 1-kb insert corresponding to mouse thymidylate synthase (E.C. 2.1.1.45). The open reading frame of 921 nucleotides from the first AUG to the termination codon specifies a protein with a molecular mass of 34,962 daltons. The predicted amino acid sequence is 90% identical with that of the human enzyme. The mouse sequence also has an extremely high degree of similarity (as much as 55% identity) with prokaryotic thymidylate synthase sequences, indicating that thymidylate synthase is among the most highly conserved proteins studied to date. The similarity is especially pronounced (as much as 80% identity) in the 44-amino-acid region encompassing the binding site for deoxyuridylic acid. The cDNA sequence also suggests that mouse thymidylate synthase mRNA lacks a 3' untranslated region, since the termination codon, UAA, is followed immediately by a poly(A) segment.      

Idiotypic replica of an anti-human tumor-associated antigen monoclonal antibody. Analysis of monoclonal Ab1 and Ab3 fine specificity

CaMBr1 is a tissue-specific and tumor-associated saccharidic epitope, defined by mAb MBr1 (Ab1), expressed on glycoconjugates of the human mammary carcinoma cell line MCF-7 and of normal and neoplastic mammary epithelial cells. An anti-anti-idiotypic monoclonal Ab3, 2G-3, identifying a human breast tumor associated antigen, was raised by using as immunogen a mouse anti-idiotypic monoclonal Ab2, A3B10, which behaves as the internal image of CaMBr1. mAb 2G-3, as well as MBr1, defines a saccharidic epitope on glycoconjugates extracted from MCF-7 cells and shows MBr1-like reactivity on normal and neoplastic-tissues. Experimental evidence, however, suggests that the fine immunoreactivity of the two antibodies is not identical, because MBr1 has a preferential reactivity with glycolipids and 2G-3 with glycoproteins. We suggest that a possible biologic explanation for our findings could reside in the nature of the immunogens used to raise the two mAb (glycolipid vs protein "internal image").     

Genome plasticity during seed germination in Festuca arundinacea

 Feulgen/DNA cytophotometric determinations were carried out on early prophases in the meristems of seedlings obtained by germinating seeds of different accessions of Festuca arundinacea at 10°C, 20°C, or 30°C. Feulgen/DNA contents increased significantly with the increase in the temperature of seed germination. In each accession, the greater the increase in absorption in seedlings obtained at 30°C, the lower the absorption in seedlings obtained at 10°C. In contrast, Feulgen/DNA contents did not undergo changes when the temperature was altered at developmental stages other than seed germination. The results of molecular hybridizations (slot blots) indicated that the redundancy of repeated DNA sequences belonging to two families having C_ot ranges of 0–2×10^-1 and 2×10^-1 −2×10⁰, respectively, was significantly higher in the genome of seedlings obtained at 30°C than in that of seedlings obtained at 10°C. When centrifuged to equilibrium in CsCl density gradients, the DNA extracted from seedlings obtained at 30°C formed a heavier and a lighter shoulder with buoyant densities of 1.707 g/ml and 1.692 g/ml, respectively, in addition to the main band (1.701 g/ml). Only a less apparent shoulder banding at 1.706 g/ml was formed by the DNA extracted from seedlings obtained at 10°C. After seed germination in the presence of [³H]-thymidine for 24 h at 30°C, most of radioactivity was found in the guanine + cytosine- or adenine+thymine-enriched DNA fractions, which formed the two shoulders in the density profile. In contrast, only guanine+cytosine-enriched fractions, which formed the heavier shoulder, were preferentially labelled in the DNA from seedlings obtained at 10°C. These results prove that fluid domains do exist in the nuclear DNA of F. arundinacea. These DNA domains are capable of rapid, quantitative alterations, which represent the direct responses of the genome to developmental and environmental stimuli. Seed germination appears to be a limited, specific period in development within which the adaptive response to temperature variations can be put into effect. Received: 9 August 1996 / Accepted: 23 August 1996